| Literature References | 1. BITO, H., DEISSEROTH, K. AND TSIEN, R.
Ca2+-dependent regulation in neuronal gene expression.
CURR.OPIN.NEUROBIOL. 7 419-429 (1997).
2. DUNLAP, K., LEUBKE, J. AND TURNER, T.
Exocytotic calcium channels in mammalian central neurons.
TRENDS NEUROSCI. 18 89-98 (1995).
3. AHLIJANIAN, M., WESTENBROEK, R. AND CATTERALL, W.
Subunit structure and localization of dihydropyridine-sensitive calcium
channels in mammalian brain, spinal cord, and retina.
NEURON 4 819-832 (1990).
4. WITCHER, D., DE WAARD, M., SAKAMOTO, J., FRANZINI-ARMSTRONG, C.,
PRAGNELL, M., KAHL, S. AND CAMPBELL, K.
Subunit identification and reconstitution of the N-type Ca2+ channel complex
purified from brain.
SCIENCE 261 486-489 (1993).
5. BURGESS, D., GEFRIDES, L., FOREMAN, P. AND NOEBELS, J.
A cluster of three novel Ca2+ channel gamma subunit genes on chromosome
19q13.4: evolution and expression profile of the gamma subunit gene family.
GENOMICS 71 339-350 (2001).
6. BURGESS, D., DAVIS, C., GEFRIDES, L AND NOEBELS, J..
Identification of three novel Ca(2+) channel gamma subunit genes reveals
molecular diversification by tandem and chromosome duplication.
GENOME RES. 12 1204-1213 (1999).
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| Documentation | Voltage-dependent calcium channels are a diverse family of proteins that
encompass a variety of biological functions, including presynaptic
neurotransmitter release and protein signalling within the cell [1,2]. The
high voltage-activated (L-, N-, P-, Q- and R-type) channels comprise the
alpha-1 subunit, which creates the pore for the import of extracellular
calcium ions [2]. The activity of this pore is modulated by 4 tightly-
coupled subunits: an intracellular beta subunit; a transmembrane (TM) gamma
subunit; and a disulphide-linked complex of alpha-2 and delta subunits,
which are proteolytically cleaved from the same gene product [3,4].
The voltage-dependent calcium channel gamma (VDCCG) subunit family consists
of at least 8 members, which share a number of common structural features
[5]. Each member is predicted to possess 4 TM domains, with intracellular
N- and C-termini. The first extracellular loop contains a highly conserved
N-glycosylation site and a pair of conserved cysteine residues. The
C-terminal 7 residues of VDCCG-2, -3, -4 and -8 are also conserved and
contain a consensus site for phosphorylation by cAMP and cGMP-dependent
protein kinases, and a target site for binding by PDZ domain proteins [5].
The VDCCG-5 subunit was identified by genomic database searching, pursuing
sequences similar to VDCCG-1 and -2 [6}. Mouse, human and rat isoforms have
been cloned. VDCCG-5 is expressed in a range of tissues, including brain,
kidney and testis [5].
VDCCGAMMA5 is a 3-element fingerprint that provides a signature for the
voltage-dependent calcium channel gamma-5 subunits. The fingerprint was
derived from an initial alignment of 3 sequences: the motifs were drawn
from conserved regions spanning the N-terminal third of the alignment,
focusing on those sections that characterise the VDCCG-5 subunits but
distinguish them from other family members - motif 1 encodes part of the N-
terminus and the N-terminal portion of TM domain 1; motif 2 resides in TM
domain 1; and motif 3 lies in the first extracellular loop. Two iterations
on SPTR40_20f were required to reach convergence, at which point a true set
comprising 4 sequences was identified.
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